Lysozyme is a newly discovered mediator of sepsis that has been shown to produce vasodilation and myocardial depression in canine models of septic shock (1-7). Lysozyme produces vasodilation by intrinsically generating hydrogen peroxide (H2O2) that leads to activation of signaling pathways resulting in these hemodynamic effects (7). In recent in-vitro studies, we showed that the antioxidants, ethyl gallate, methyl gallate, and ethyl 3,4-dihydroxybenzoate blocked the effect of lysozyme on producing vasodilation in a canine carotid artery preparation. We thought that ethyl gallate showed the most promising response.
Ethyl gallate is added to food as an antioxidant. It is the ethyl ester of gallic acid. Though found naturally in a variety of plant sources including walnuts (8), ethyl gallate is produced from gallic acid and ethanol (9). Moreover, it should be noted that in the above investigations, other potential inhibitors of lysozyme's vasodilatory response, some of which are known to have antioxidant properties, such as gallic acid, propyl gallate, sodium benzoate, limonene, quercetin dihydrate, guaicol, curcumin, ellagic acid, epicathechin gallate from green tea, catechin gallate, epigalloccatechin gallate from green tea, polypheno 60 from green tea, crocin, luteolin, sodium ascorbate, N-acetylcyteine, reduced glutathione, among others, all failed to block lysozyme's vasodilatory effect in the carotid artery preparation. Thus, ethyl gallate, methyl gallate, and ethyl 3,4 dihydroxybenzoate has unique properties for the treatment of septic shock. It is of note that if a substance could not inhibit lysozyme's effect in-vitro, then it would be worthless to pursue an in-vivo study. Even so, the fact that a substance can work in-vitro does not necessarily mean that it will work in-vivo. For instance, mannitol worked in the in-vitro preparation, but did not have a positive effect in-vivo.